Difference Between Megaloblastic and Pernicious Anemia

Main Difference – Megaloblastic vs Pernicious Anemia

Anemia is a general form used to define the low level of Hemoglobin in blood. Megaloblastic anemia and Pernicious anemia are two types of anemia. Megaloblastic anemia is  a type of macrocytic anemia which occurs as a result of the inhibition of DNA synthesis during red blood cell production. Pernicious anemia is a form of megaloblastic anemia, which occurs due to lack of vitamin B12. This is the main difference between megaloblastic and pernicious anemia. 

This article covers,

1. What is Megaloblastic Anemia? – Causes, Signs and symptoms, Diagnosis and Treatment
2. What is Pernicious Anemia? – Causes, Signs and symptoms, Diagnosis and Treatment
3. What is the difference between Megaloblastic and Pernicious Anemia?

Difference Between Megaloblastic and Pernicious Anemia - Comparison Summary

What is Megaloblastic Anemia

Megaloblastic Anemia is defined as a type of macrocytic anemia which occurs as a result of the inhibition of DNA synthesis during red blood cell production. The ultimate disruption in cell growth due to impaired division microscopically present as macrocytosis. Compared to other types of anemia, Megaloblastic anemia usually has a slow onset and rapid progression.

As far as the major cause for this condition is concerned, the characteristic defect in red cell DNA synthesis is mostly due to hypovitaminosis, especially as a result of vitamin B12 and folic acid deficiency. However, Vitamin B12 deficiency alone will not be able to produce the signs of the syndrome if there is a sufficient amount folate.  This is why Folic acid supplementation in the absence of vitamin B12 can often prevent Megaloblastic anemia.

Major causes for the deficiency of Vitamin B12

  • Reduced dietary intake
  • Malabsorption due to conditions like Achlorhydria
  • Coeliac disease
  • Intrinsic factor deficiency which is essential for the absorption of vitamin B12
  • Chronic Pancreatitis
  • Ileal resection and anastomosis

Major causes for Folic acid deficiency

  • Chronic alcoholism
  • Reduced intake
  • Increased demand- pregnancy, infancy
  • Congenital or drug-induced malabsorption
  • Jejunal resection
  • Inherited DNA synthesis disorders

In addition, deficiency of micronutrients like Copper is also known to be a well-known reason for this condition to develop.

Patients with this condition will experience general features of anemia such as shortness of breath, chest pain, palpitation, fatigue, and malaise. There will also be signs like glossitis and smooth tongue appearance.

A full blood count in suspected patients will reveal reduced Hemoglobin levels with an increased MCV count, revealing a macrocytosis. A peripheral blood smear will further confirm the diagnosis with the presence of hypersegmented neutrophils, Anisocytosis, and poikilocytosis.

Moreover, a biochemical analysis will show an increased lactic acid dehydrogenase (LDH) level (typical of serum and hematopoietic cells), raised levels of Homocysteine and methylmalonic (Vitamin B12 deficiency) and homocysteine (folate deficiency).

The treatment will be based on the etiology which will have to be addressed individually. If there is a reduction of intake, dietary or supplementary intake should be encouraged.

Difference Between Megaloblastic and Pernicious Anemia - 1

What is Pernicious Anemia (PA)

This is defined as a type of megaloblastic anemia, which occurs due to lack of vitamin B12 secondary to malabsorption as a result of intrinsic factor deficiency, a compound secreted by the inner mucosal lining of the intestines.

This may occur due to various underlying conditions such as autoimmunity and drugs. The commonest complication with untreated PA is the impairment of neurological functions since Vitamin B12 is a compulsory factor needed for the development of neurons.

Therefore the most usual signs and symptoms of this condition include, tingling sensation and numbness in the hands and feet, malaise, fatigue and bright red smooth tongue.

Patients with clinical signs and symptoms suggestive of PA can be diagnosed with a full blood count which will show low Hemoglobin, high MCV, and normal MCHC, suggestive of macrocytic anemia.

A peripheral blood smear can be done next, which will often show large, fragile, immature erythrocytes, known as megaloblasts, Ovalocytes and hypersegmented neutrophils (common to all megaloblastic anemia).Reduced Serum B12 levels will further confirm the diagnosis.

Treatment for PA usually depends on the underlying etiology and neurological impairments should be addressed promptly to prevent severe complications.

High dose of Vitamin B 12, given orally has found to be effective in most patients, but some will only respond to intramuscular injections containing Cyanocobalamin which is the treatment of choice for PA.

Main Difference -Megaloblastic vs Pernicious Anemia

Difference Between Megaloblastic and Pernicious Anemia

Pernicious Anemia is a form of megaloblastic anemia (caused by vitamin B12 or folic acid deficiency or both) which occurs due to reduced level of Vitamin B12 in the body secondary to malabsorption mostly as a result of reduced or absent intrinsic factor.

Both will show hypersegmented neutrophils on the peripheral blood smear whereas PA will characteristically reveal Ovalocytes.

Image Courtesy:

“Hypersegmented neutrophil” (Public Domain) via

“Hydroxocobalamin Injection” By Sbharris – Own work via

About the Author: Embogama

Embogama is a passionate freelance writer for several years. Her areas of interest include general medicine, clinical medicine, health and fitness, Ayurveda medicine, psychology, counseling and piano music


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